ЖУРНАЛ АНАЛИТИЧЕСКОЙ ХИМИИ, 2014, том 69, № 10, с. 1029-1035
ОРИГИНАЛЬНЫЕ СТАТЬИ
УДК 543
SIMULTANEOUS DETERMINATION AND VALIDATION OF SOME BINARY MIXTURES OF ANTIHYPERTENSIVE DRUGS USING RATIO DERIVATIVE
SPECTROPHOTOMETRIC METHOD
© 2014 Sevinc Kurbanoglu*, Mehmet Gumustas*, **, Sibel A. Ozkan*, 1
*Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry 06100, Tandogan, Ankara, Turkey 1E-mail: ozkan@pharmacy.ankara.edu.tr **Hitit University, Science and Literature Faculty, Department of Chemistry
Corum, Turkey Received 20.08.2012; in final form 16.05.2013
Keywords: hydrochlorothiazide, olmesartan, ratio derivative spectrophotometry, zofenopril. DOI: 10.7868/S0044450214100120
Ratio derivative spectrophotometric technique is presented for the rapid, accurate and precise simultaneous determination of olmesartan medox-omil (OLM), hydrochlorothiazide (HCT), and zofenopril (ZOF) as well as HCT binary mixtures in their dosage forms. First derivative of the ratio spectra (DDj) by measurements using different amplitudes was used and calibration graphs were established for 0.5—12 ^g/mL HCT and 0.5— 20 ^g/mL OLM and ZOF. This method depends on first derivative of the ratio spectra by division of the absorption spectrum of the binary mixture by a standard spectrum of one of the components and then calculating the first derivative of the ratio spectrum. The first derivative of the ratio amplitudes at 250.4 and 291.5 nm for OLM, 250.4 and 298.1 nm for ZOF and 231.8, 332.2, 232.3 and 280.4 nm for HCT were selected for the determination. The proposed methods were successfully applied for determining of both drug combinations (ZOF—HCT and OLM—HCT) in their synthetic mixtures and in pharmaceutical dosage forms. The described procedures are extensively validated, non-destructive and do not require any separation steps.
Hydrochlorothiazide, (Scheme) 6-chloro-3,4-di-hydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide, is a thiazide diuretic that is frequently used for the treatment of hypertension and congestive heart failure [1—3]. Olmesartan medoxomil is a prodrug hydrolyzed to olmesartan during absorption from gastrointestinal tract. It is chemically described as cyclic 2,3-carbonate, 2,3-dihydroxy-2-butenyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidozole-5-carboxy-late. OLM is an angiotensin II receptor antagonist. The main effect mechanism of OLM is lowering the blood pressure [1—3]. Zofenopril calcium is also a prodrug that is deesterified to the active inhibitor, the sulfhydryl group containing compound, zofenopri-lat. [1(s), 4(s)]-1-(3-mercapto-2-methyl-1-oxopro-pyl)-4-phenyl-thio-L-proline-S-benzoylester that is a new sulfhydryl-group containing angiotensin converting enzyme inhibitory drug. It has a high potential in the prevention and therapy of cardiovascular diseases [1—3]. The binary mixtures of HCT with OLM or ZOF cause a greater drop in blood pressure than when either medicine is used alone. These combinations are widely used in the treatment of hypertension [1—3].
1030
SEVINC KURBANOGLU и др.
O.
O
HO
N
(a)
HO
Cl
// \\ O O
(b)
л
O O
,NH
(c)
Molecular structure of zofenopril (a) olmesartan medoxomil (b) hydrochlorothiazide (c).
S
Several methods have been reported concerning simultaneous determination of OLM and HCT [4—13] in pharmaceutical dosage form or biological samples using UV-spectrophotometric [4-6], LC-MS/MS [7], TLC and HPTLC [8-10], and LC [10-13]. Even though some procedures have been described for the assay of either ZOF or HCT in dosage forms, there are only limited methods such as LC [14, 15] and derivative spectrophotometry [16] able to determine ZOF and HCT simultaneously [16]. No method for the simultaneous analysis of binary mixtures of OLM-HCT and ZOF-HCT has been cited in any pharmacopoeia. Also, in literature survey, a suitable method could not be found that is sensitive for routine analysis of dosage forms.
The simultaneous determination of the two compounds is often a difficult task for the analyst and the problem is even more complicated if these compounds are included in a pharmaceutical dosage form where excipients are interfering. The direct UV-spectropho-tometric method presents several problems including the spectral bands of both OLM-HCT and ZOF-HCT overlap. The ratio-spectra derivative spectrophotometry (DD1) method [17-20] has been found to be useful for the estimation of drugs in their mixtures. The use of the derivative spectrophotometric method for resolving a mixture with overlapped spectra produces a considerable loss of accuracy and sensitivity. The ratio derivative spectrophotometric method permits the determination of a component in their mixture at the wavelengths corresponding to a maximum or minimum of the ratio derivative spectrum. The main advantage of this method may be the chance of doing easy measurements in correspondence of peaks so it allows the use of the highest response value of the analytical signals.
The goal of this study is the development of new, rapid, selective, accurate, precise, sensitive, fully validated method for the simultaneous and direct determination of OLM-HCT and ZOF-HCT binary mixtures in raw materials and film coated tablet dosage forms without any time-consuming extraction or evaporation steps prior to the assay. Ratio derivative spectrophotometric method has been developed for the simultaneous determination of the selected binary mixtures. These spectrophotometric studies were therefore aimed to provide an economically viable method for the routine control laboratories.
EXPERIMENTAL
Instruments. A Shimadzu 1601 PC double beam spectrophotometer equipped with 1.0 cm quartz cells with a fixed slit width (2 nm) was used, coupled with a computer running spectrophotometric software Shimadzu UVPC software.
Chemicals and reagents. All chemicals and solvents were of analytical reagent grade. Olmesartan medox-omil, hydrochlorothiazide and zofenopril calcium and their binary pharmaceutical dosage forms were kindly provided by Abdi Ibrahim and I.E. Ulagay Pharm. Ind. (Istanbul, Turkey).
Stock and working solutions. Stock solutions of OLM, ZOF, HCT and IS (1.0 mg/mL) were prepared by dissolving 10.0 mg of each compound in 10 mL methanol (1000 ^g/mL stock) and the standard solutions were prepared individually by dilution of the stock solutions with methanol to reach a concentration range of 0.5-20 ^g/mL for OLM and ZOF and 0.5-12 ^g/mL for HCT. The absorption spectra of the binary mixtures prepared at different concentration of the compounds were recorded and stored.
For the simultaneous determination of binary mixtures of OLM and HCT, the stored spectra of the standard solutions of OLM were divided, wavelength by wavelength by a standard spectrum. Then the 1st derivatives of the ratio spectra were recorded and the values of the derivatives were measured at suitably selected wavelengths in the range of 200—400 nm by plotting against the corresponding concentrations to obtain the calibration graph. The amplitudes were measured and found to be linear to the concentration of analyte.
All solutions were protected from light, stored at +4°C and used within 24 h avoid decomposition. However, chromatograms and spectra of the sample solutions recorded over a weak period after preparation but no considerable change in assay values were observed.
Analysis of pharmaceutical dosage forms. Each Zo-protec® Plus film-coated tablets contain 30 mg zofeno-pril calcium, 12.5 mg hydrochlorothiazide and the inactive ingredients lactose monohydrate, titanium dioxide (E171) and red ferrioxide (E172). Each Olmetec® Plus film coated tablets contain 20 mg Olmesartan medoxomil, 12.5 mg hydrochlorothiazide and the inactive excipients microcrystalline cellulose, hydrox-ypropyl cellulose, lactose monohydrate, magnesium stearate, hydroxylpropoylmethylcellulose, talc, titanium dioxide (E171), yellow and red iron(III) oxide (E172). For the assay of both binary mixtures, 10 tablets were accurately weighed, crushed and finely powdered. A weight of the powder equivalent to one tablet content was accurately weighed, transferred into 50 mL calibrated flask, diluted with methanol, sonicated about 10 min and then completed to total volume with methanol. This solution was filtered and the filtrate was collected in a clean flask. After filtration, solutions were prepared by taking suitable aliquots of the clear filtrate and diluting them with methanol in order to obtain a final solution. The content amounts of these drug active compounds were calculated from the corresponding regression equations.
Recovery studies from tablets and laboratory made mixtures. In order to demonstrate the applicability of the proposed DD1 method, the recovery studies were realized by analyzing laboratory-made mixtures of OLM—HCT and ZOF—HCT couples. After eight repeated experiments, the recovery results were calculated and reported for each compounds and all responded techniques.
To verify the accuracy of the proposed method, recovery experiments were also carried out by adding known amount of pure drug to the pre-analyzed tablets. The percent recovery results were calculated by comparing the concentration obtained from spiked samples with the actual added concentration. Thus, the effect of common excipients in film coated tablet dosage forms on spectra was studied.
Wavelength, nm
Fig. 1. (a) — Absorption spectra of 6.25 p.g/mL HCT (1), 10 p,g/mL OLM (2) and a mixture of OLM (10 ^g/mL) and HCT (6.25 p,g/mL) in methanol (3). (b) — Absorption spectra of 6.25 ^g/mL HCT (1), 15 ^g/mL ZOF (2) and a mixture of ZOF (15 p,g/mL) and HCT (6.25 p,g/mL) in methanol (3).
RESULTS AND DISCUSSION
OLM and HCT binary mixtures have already been studied using DD1 method [5] in 0.1 M NaOH solutions, while ZOF—HCT mixture has not yet analyzed with that method. Also, OLM—HCT and ZOF—HCT mixtures are not yet officially found in any ph
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